The goal is to study human leukemias and non-Hodgkin's lymphomas using a multidisciplinary approach encompassing morphology, immunologic markers, cytogenetics, and flow microfluorometric analysis of DNA content, cell size, and cell kinetics in order to improve characterization and classification of these diseases. Cell suspensions and frozen tissues from more than 750 cases of non-Hodgkin's lymphomas, lymphocytic leukemias, and reactive lymphoproliferative conditions have been studied during the past year. We measured adenosine deaminase and purine nucleoside phosphorylase activities by using a linked enzyme spectrophotometric assay on peripheral blood leukemia cells from seven patients with chronic lymphocytic leukemia, three patients with prolymphocytic leukemia and one patient with prolymphocytoid transformation of chronic lymphocytic leukemia. Our studies suggest that purine nucleoside phosphorylase activity in leukemic cells may be useful in distinguishing prolymphocytic leukemia from chronic lymphocytic leumemia, and that it may be an enzymatic marker for the early detection of prolymphocytoid transformation of chronic lymphocytic leukemia. We have described the presence of monocytoid B lymphocytes (MBL) in 17 of 22 lymph nodes from 20 patients with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-related lymphadenopathy. In all 17 samples, the MBL were found in lymph nodes showing florid reactive follicular hyperplasia. MBL were not detected, however, in lymph nodes showing involuted follicles or lymphocyte depletion. Disappearance of MBL apparently parallels the progressive involution of secondary follicles. The diminished T-helper status in AIDS may be relevant to the pathogenesis of follicular involution and indirectly to the disappearance of MBL. Peripheral T-cell lymphomas (PTCL) have been shown to be a morphologically heterogenous group of non-Hodgkin's lymphomas. We have studied PTCL occurring in a 13-year-old girl from whom we were able to evaluate histologic material from 11 biopsies obtained during her 8-month clincial course. These biopsies demonstrated morphologic progression from atypical immune reactions (AIR) and diffuse mixed cell lymphoma (DM) at the time of clinical diagnosis to pleomorphic large cell lymphoma (LCL) with erythrophagocytic tumor cells at the time of her death. We conclude that morphologic progression in PTCL is expressed, in sequential biopsies, by a progressive cellular pleomorphism with the appearance of large, often bizarre lymphoid cells, and the gradual diminuition and disappearance of the B-cell areas and epitheloid histiocytic areas which were present initially. (4)